chr22-37234748-T-C

Position:

• chr22-37234748-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002872.5(RAC2):​c.108-1830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,256 control chromosomes in the GnomAD database, including 59,299 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (59299 hom., cov: 32)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99

Genes affected

RAC2 (HGNC:9802): (Rac family small GTPase 2) This gene encodes a member of the Ras superfamily of small guanosine triphosphate (GTP)-metabolizing proteins. The encoded protein localizes to the plasma membrane, where it regulates diverse processes, such as secretion, phagocytosis, and cell polarization. Activity of this protein is also involved in the generation of reactive oxygen species. Mutations in this gene are associated with neutrophil immunodeficiency syndrome. There is a pseudogene for this gene on chromosome 6. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.108-1830A>G		intron_variant		ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.108-1830A>G		intron_variant			XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.108-1830A>G		intron_variant		1	NM_002872.5	ENSP00000249071	P1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 134058 AN: 152138 Hom.: 59257 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.881 AC: 134151 AN: 152256 Hom.: 59299 Cov.: 32 AF XY: 0.880 AC XY: 65525 AN XY: 74426

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.868

Gnomad4 OTH AF: 0.868

Alfa AF: 0.863 Hom.: 38336

Bravo AF: 0.875

Asia WGS AF: 0.844 AC: 2936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1476002; hg19: chr22-37630788;